Ethical issues in genetic medicine
Academic Unit of Genetic Medicine, University of Southampton, UK
E-mail: a.m.lucassen{at}soton.ac.uk
‘It is in the genes’ is an expression commonly used by patients in the surgery. The use of genetic information in general practice has become more common place in recent years. Family history is recorded as part of new patient checks and it is usual to ask patients with symptoms suggestive of a disease with a genetic component about family history of that disease and other potentially related diseases.
General practitioners are well placed to practice genetic medicine for a variety of reasons: Primary care has long recognized the multifactorial origins of disease and its practice lays a strong focus on identification of those at risk of a particular disease and prevention or early detection of disease. Screening programmes for genetic diseases, risk based screening for common diseases with a genetic component and pharmacogenetics are all set to enter routine medical practice. GPs' roles as the family doctor means that the family centred care required by genetic medicine will be familiar to them. Nevertheless, there are potential tensions also. Genetic information about one person may have implications for their relatives. How does the traditional ‘family-based’ approach accommodate an increasing focus on autonomy and confidentiality in today's society while appropriately informing others at risk?
Many patients have a keen interest in genetics, but some have unrealistic expectations of what genetics can offer and believe it to be more deterministic than it is. Others view genetic testing with a degree of suspicion or worry. It is important that GPs understand the issues involved so that they can explain clearly the advantages and pitfalls of genetic testing to support patient choices.
Through a series of case histories illustrating dilemmas that may arise in practice, this article aims to raise and discuss some of the ethical issues in genetic medicine that a GP may encounter. The cases are derived from real cases but have been altered to preserve anonymity. They have been chosen to highlight ethico-legal dilemmas and therefore do not necessarily have one correct answer. It is hoped that thinking about such cases will encourage a wider debate about how to integrate genetic medicine into routine medical care.
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Statement 3.3 of the GP curriculum is concerned with ethics in primary care and Statement 6 with genetics. It requires GPs in training to be able to apply ethical principles to practical situations in primary care. In particular, GPs in training should be able to:
Statement 6 requires GPs to describe how genetic information impacts not only on patients but also on their immediate and extended family. Statement 3.3 requires the GP to be able to balance conflicting duties to individual patients who are members of the same family.
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Taking a family history |
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The family tree is an important clinical tool for answering questions about a patient's risk of developing a genetic disorder and appropriate management. Unlike most medical records, family tree records can contain sensitive information not only about the patient, but also about other family members. The tacit assumption has been that this information is ‘hearsay’ and in the public domain because it has been shared within the family. Therefore, explicit consent to record information about family members, particularly if they have had no contact with services, has not been routinely sought (Joint Committee on Medical Genetics, 2006). However, the advent of data protection legislation and the prospect of unified patient electronic records that can be accessed from multiple locations has raised questions about the legitimacy and limits of such practice. If others are identifiable from a family tree when should they be told about genetic information that might be relevant to them, how should they be told and by whom? Such issues will be most acute if a doctor looks after several different family members and therefore owes them all a duty of care. If risk information is not communicated within a family, then there may be a tension between appropriately informing one person yet keeping the confidence of another.
| Case history 1: Patient autonomy and the right to confidentiality Andrew has an inherited form of bowel cancer (HNPCC) confirmed on DNA testing. He is very ill with advanced colorectal cancer. Andrew has several siblings with whom he is not in regular contact. In giving his family history, Andrew has told the genetics doctor the names, dates of birth and residence of his brothers and sisters. However, he is reluctant to tell his siblings about his own results. He does not appear to be withholding this information maliciously but because of the lack of contact finds it difficult to approach them and he has many other things on his mind. The genetics department have offered Andrew help to make contact with his siblings but Andrew has declined and said he will do it but would just like to get over his current treatment first. Andrew's GP also looks after other members of the family but does not want to disclose any risk information to them without Andrew's consent. A year later Andrew's brother, Peter, presents, aged 39, with a Duke's C bowel cancer. Peter had not had any bowel screening and had not realized he was at increased risk of young onset cancer. Questions:
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Identifying others at risk
Once relatives have been identified in a family tree, the clinician may become aware of people who are also at risk of a particular condition who may not know this themselves. Once Andrew's genetic test result was known, it became apparent that his siblings had a 50% chance of having inherited the same cancer predisposition. Genetic services in the UK and other countries usually ask an individual to share their genetic information with relatives to whom it may be relevant and may offer support mechanisms to work with families and their doctors to ensure that people at risk are appropriately informed. Depending on family structure and circumstances, such communication can happen effectively, but at other times less so. The latter is difficult to assess because there may be a variety of reasons why relatives do not present to a genetics service. They may have received the relevant information but not wish to pursue genetic testing or they may live in another part of the country or world and therefore their attendance will not come to the attention of Andrew's genetic team. The non-disclosure of genetic test results has been described and researched and empirical data has demonstrated a fall off in disclosure with emotional distance (Julian-Reynier et al., 2000; Claes et al., 2003). Although a survey of cases in a variety of genetic centres suggested that persistent non-disclosure is rare, this study only examined cases where healthcare professionals were made aware of it (Clarke et al., 2005).
The challenge is how to deal with a situation like Andrew's, when doctors know the identity of people at risk but consent to communicate that risk has not been obtained. Both professional guidelines and UK case law recognize that Andrew's confidentiality can be breached legitimately if considered in the public interest since a concern about a (preventable) harm to others places a limitation on the duty of confidentiality (GMC: Duties of a Doctor, 2000; W v Egdell, 1990). While it can be argued that disclosure to Andrew's brother would have allowed colonoscopic surveillance and that a harm (of presenting with advanced cancer) might thereby be prevented, Andrew's brother was born with the inherited tendency and this could not have been prevented by a breach of confidentiality. A preventable harm argument in genetics is therefore slightly different from the legal precedents for this situation. There is no UK case law about genetic disclosure, but US courts have made opposing decisions, with one concluding that a doctor should have informed relatives despite the insistence of the affected person that he did not (Pate v Threlkel, 1995; Safer v Pack, 1996).
The traditional genetic practice of asking patients to communicate their familial risks with their relatives acknowledges the personal and potentially sensitive nature of genetic information and the difficulties of approaching individuals who have not been referred or asked about their own risks. It also arose at a time when there were few interventions or managements to offer those at risk. More recently, as evidence-based effective interventions for particular genetic conditions have developed, direct communication between the medical professional and family members at risk has been trialled and found successful and acceptable (Suthers et al., 2006; Aktan-Collan et al., 2007). However, this has not yet been routinely adopted in UK practice, not least because of the significant workforce and financial implications. Furthermore, these studies relied on the consent of the patient and does not therefore address what to disclose to Andrew's relatives without such consent.
Breaching confidentiality to prevent serious harm in others is likely to rely on the availability of an effective intervention. In this case, regular colonoscopy and early adenoma removal is likely to significantly reduce the morbidity and mortality of HNPCC. In other genetic conditions, the evidence basis is less clear or absent. However, alternative interventions such as prenatal diagnosis or childbearing choices might be affected by the communication of genetic information; so a careful discussion of appropriate management will be needed in many families even in conditions for which there is no treatment.
In many cases like these, working with Andrew to highlight the importance of disclosure while offering good support will help solve the dilemma. Alternative routes might also be explored. It might be possible to warn Andrew's relatives of their risk in an anonymized way without breaching Andrew's confidentiality. If there was a further family history of bowel cancer, then this could perhaps be used as a reason to screen Andrew's brother.
Individual or familial confidentiality?
Andrew's case highlights the tension between preserving individual confidentiality and communication of genetic risk to others. The Human Genetics Commission's 2002 report suggested that ‘genetic solidarity’ and altruism should be promoted (Human Genetics Commission, 2002), and several authors have challenged the supremacy of individual autonomy in genetic medicine and introduced versions of family rather than individual confidentiality (Doukas and Berg, 2001; Davey et al., Parker and Lucassen, 2004). For example, the joint account model argues that since genetic information is shared by more than one person, the conventional model of confidentiality should be reversed: the genetic information should be available to all ‘account holders’ (family members) unless there are good reasons to do otherwise. Thus, genetic information discovered through one person may be considered familial rather than individual and should be shared with others for whom it has relevance, unless there is a very good reason not to (Lucassen and Parker, 2006).
These models are useful in encouraging a different perspective towards genetic information and reflect that most individuals availing themselves of genetic medicine do so with some degree of altruism.
| Case history 2: Finding unexpected information David and Susan are seen in the genetic clinic after a severe autosomal recessive condition was diagnosed in their newborn baby. They are counselled about a one in four recurrence risk and told that prenatal testing would be possible in a future pregnancy if the causative mutations can be found. The baby is tested and two mutations are found in the relevant gene. In order to clarify that these mutations lie on different chromosomes (and that thus the true cause of the condition has been found), the parents consent to each give a blood sample to determine if they are both carriers of the causative gene. Tests on these samples reveal that husband is not biological father of the child. Question: Should this unexpected result be revealed to Susan and/or David when they come back to the clinic?
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In this case, the family history suggests that both parents are carriers of the condition and they will have a one in four chance of having another child together with the same condition. Both parents were counselled about this at the time of the baby's diagnosis. However, if David is not the baby's father, then the chance that David and Susan together will have an affected child is zero.
Debates about whether or not to disclose a finding of misattributed paternity often assume it is an incidental finding that has no bearing on the management of a condition. Because of the sensitive nature of the finding, many health professionals would prefer not to disclose, would fudge or even lie if questioned directly about it. Some would advocate telling Susan alone and to leave any further disclosure to her (Pencarinha et al., 1992; Wertz et al., 1990).
However, in this example, the result has a direct bearing on the management of the case. The information has reproductive implications for both David and Susan and both are your patients. They attended the clinic together for information about an issue of joint concern. For these reasons, the test result is confidential to the couple, not just to one of them. To inform Susan alone would not properly respect John's right to this information and treats him inequitably. Although the law makes it clear that only the woman has the right to choose whether to have prenatal testing and whether or not to terminate the pregnancy, the situation here is different because the test result carries information about David and the doctor has a duty of care to David as well as Susan in this case.
Therefore, in this particular set of circumstances, not disclosing the result is problematic because:
- The couple cannot then make autonomous choices
- Without accurate information, the couple may make misinformed choices (they may go on to have risky prenatal testing in a future pregnancy or decide not to have children at all)
- Not to inform the couple is unjustifiably paternalistic
At the same time, rushing in to explain that paternity was not as had been implied would clearly also be inappropriate. There are rare genetic mechanisms that can present like non-paternity or there could have been a sample mix-up. While there is no easy answer to this dilemma, good practice suggests that in situations where genetic testing could reveal non-paternity (it should be noted that most genetic tests will not determine parentage), this should be raised at the outset. Raising the possibility before genetic testing reduces the ethical dilemmas encountered when such tests do in fact reveal that parentage is not as stated. However, this is not an easy task and will need to be approached sensitively and appropriately (Lucassen and Parker, 2001).
| Case history 3: Genetic testing of children and indirect genetic testing John is 25 and seen in the genetics clinic after a diagnosis of Huntington's disease (HD) has been made in his 45-year-old mother and confirmed molecularly. John is informed that a highly accurate predictive test is available and that there is a 50% chance that he has inherited the condition. After lengthy discussions, John decides that he does not wish to know whether he has inherited HD. His main reasons for this decision are the lack of effective treatment and the long-time interval till the likely onset of symptoms. Some time later his girlfriend, Sarah, attends with their 4-year-old son, Ben. Sarah would like Ben to be tested as she has observed the ‘awfulness’ of HD in John's family and would like to be prepared if Ben has inherited HD. Questions: Should Ben be tested? Does John's refusal of a test have any bearing on the decision whether or not to test Ben?
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Once a disease causing mutation has been identified in a family, it is perhaps not surprising that parents might want to know whether or not a child has inherited it. In 1994, guidelines were issued by the UK Clinical Genetics Society about predictive genetic testing in children (Clarke, 2004). These and other subsequent national and international guidelines recommend that, where there is no anticipated medical benefit (such as preventative or therapeutic actions that could be initiated), testing should be deferred until such time there was or the child is old enough to make an autonomous decision (Borry et al., 2006).
Much has been written about the potential psychosocial consequences of testing in the absence of medical benefit. Most of the guidelines base their conclusions on the need to protect children's best interests and that these are not served if there is no medical benefit to the testing. For an adult onset disease, a test in childhood will deny the future adult a choice in the matter and this is particularly relevant in conditions like HD where only a small proportion of adults who enquire about predictive genetic testing go on to take the test once the advantages and disadvantages have been discussed with them. Concerns have also been expressed about what effects a positive predictive genetic test in childhood might have on the relationship between parent and child, might this be associated with increased anxiety in their relationship?
On the other hand, the debate has acknowledged a wider perspective than whether or not there is a medical intervention to offer. As the Genetic Interest Group put it in response to the UK guidelines: ‘Parents are responsible for welfare of children and at the end of the day most are better equipped to decide what is in the best interests of their child and family than outsiders are’ (The Genetic Testing of Children 1995: accessed May 08 from: www.gig.org.uk/docs/gig_testingchildren.pdf). The test may have been requested to seek reassurance that Ben has not inherited the condition. At present, Ben has a 25% chance of having inherited the condition (his father is at 50% risk, Ben's risk is half this). In this case, there is therefore an extra dilemma: if Ben tests positive, John will thereby also receive his result, something that he has explicitly refused to provide consent for.
There are therefore four broad reasons for deferring/declining a test on Ben at present.
- The condition has an adult onset and there are three to four decades before the likely onset of symptoms
- There are no interventions to offer as a result of the test that would alter the course of the condition
- Testing before Ben can consent, denies him a choice as an adult (i.e. the choice that his father has just exercised)
- If Ben tests positive for HD, then he thereby reveals his father's genetic test result
Somewhat paradoxically perhaps, the situation might be different if Sarah had requested a test during pregnancy. While the ethical arguments are very similar, at this stage, the fetus is considered to be part of its mother and therefore she would have the right to choose to test. If she had a termination as a result, then John might similarly infer his own results; if she did not terminate, then a child would be born who had a genetic test result which guidelines suggest should not have been done in childhood (Lucassen and Parker, 2004). These are highly complex situations and genetics centres would have detailed discussions with John and Sarah outlining the familial implications and the potential difficulties of testing. In pregnancy, an alternative of an ‘exclusion test’ can be offered. This would not reveal John's HD status but has the disadvantage of being less able to accurately define the baby's risk, so that a ‘high-risk’ pregnancy might also include an unaffected baby.
Because of the existence of guidelines discouraging testing in childhood, there is little empirical evidence about the consequences of such testing and research is needed to know whether current guidelines are too cautious. In the meantime, where requests are made, clinicians should engage in discussions with parents about what the advantages and disadvantages of testing in childhood might be and whether or not it could be deferred until an age at which the child can take part in the consenting process. Where the onset of a condition is imminent and where an intervention is available (e.g. familial adenomatous polyposis), a different decision about testing might be made that if this is not the case (such as HD).
| Case history 4: Prenatal genetic diagnosis Emma (25) is a carrier for Duchenne's muscular dystrophy (DMD) (an X-linked condition). This was discovered some years ago following testing of her nephew who was diagnosed with the condition aged 5. She is in stable relationship and wants children. She attends the genetics unit to enquire about prenatal diagnosis. In this situation, prenatal testing is very accurate; there is a 25% chance of an affected child (half of all her sons will be affected). Emma says that she would terminate an affected boy. She does not want her husband to know about her carrier status or prenatal testing. Her husband is unaware of the family history since the affected nephew died some years ago. Questions: What are Emma's options? Does the father have any rights?
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Prenatal diagnosis can determine whether or not a fetus has inherited a condition such as DMD or an inherited predisposition to a condition such as cancer. The possibility of termination of pregnancy is usually the reason for testing at this stage. While the law would recognize a woman's right to choose to test her baby during pregnancy, independent from the wishes of and without the involvement of, her partner, a moral argument might opine that Emma's husband is thereby being kept in the dark about the risks his children are at and that he might have a right to know about this. Again, the dilemma might be more acute if her husband was also your patient and independently asked you about risks to his children.
Emma's reluctance to disclose may be attributable to a perceived stigma or fear of discrimination, and genetic counselling is often useful in this situation in facilitating discussions and allowing appropriate disclosure of information.
Discussion of alternatives to termination of pregnancy on the basis of a genetic disorder are also sometimes appropriate. Preimplantation genetic diagnosis or PGD is the testing of an embryo before implantation. While the current technical limitations of this procedure mean that the chance of a successful pregnancy is much lower than with natural conception, it is preferable to some prospective parents because termination of an existing pregnancy can be avoided. In the UK, PGD requires a license from the Human Fertilization and Embryology Authority (HFEA).
Initial licenses were for fully (or almost fully) penetrant diseases such as DMD, cystic fibrosis and HD but following a public consultation on what its policy should be for late onset conditions that are incompletely penetrant, the HFEA recommended that it would be appropriate, in principle, to extend the use of PGD for cancer genes ‘because the features of the conditions are not incompatible with them being regarded as serious genetic conditions’ (www.hfea.gov.uk). Thus, PGD or prenatal diagnosis may be applied to adult onset predispositions, which may never manifest or which may be curable by the time the embryo under consideration reached an at-risk age. These issues again need careful discussion with an expert team before any decisions are made.
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Genetic information and discrimination |
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There has been much public debate about the potential for genetic information to cause discrimination, for example, by insurance or employment agencies. The UK Human Genetics Commission has recently called for comprehensive legal protection against ‘discrimination on any genetic grounds’ (www.hgc.gov.uk). This noted that clinicians report that people are reluctant to take DNA tests that may be important for their health because of fears that test results may be used to their disadvantage by third parties such as employers or insurance companies.
The UK insurance industry has a self-imposed moratorium, initially from 2001–06, and then subsequently extended to 2011 and now 2014, that they will not ask policy holders to have a genetic test, or the results of a genetic test for policies valued at less than £500,000 for life insurance purposes and less than £300 000 for other purposes. Above these limits, only tests approved by the Genetics and Insurance Commission (www.advisorybodies.doh.gov.uk/genetics/gaic/) can be used. To date testing has only been approved for HD. However, family history of disease continues to be used to load or refuse premiums with much intercompany variation in the sophistication of family history analysis. General practitioners are often asked for medical reports to help decide premiums. Although disclosure of genetic test results should not be made in such reports, significant family histories may legitimately be disclosed, but may not be asked for by all companies.
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Where to go for help |
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TOPThe GP curriculum and...Taking a family historyGenetic information and...Where to go for...References |
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Most clinical genetics departments will have some facility for discussion of complex cases, either within their own department or in their local hospital through, for example, a clinical ethics committee (www.ethics-network.org.uk/). The UK genethics club (www.genethicsclub.org; Lucassen and Parker, 2006) holds national meetings for discussion of ethical cases or issues arising in genetic practice. This provides a forum for health professionals to explore ethical dilemmas or problems and work towards shared models of good practice.
Key points
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References |
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